Synthesis of combinatorial compound libraries on bead supports is a well-established method for generating chemical diversity for screening against targets of pharmacological relevance. Such libraries may be synthesized as bulk populations or discrete sublibraries with or without identifier tags for deconvolution. In most cases each bead carries a single unique compound and is present in a mixture of beads containing other compounds. To test the beads for activity against a pharmacological target, it is desirable to separate the beads so that each bead may be individually assayed against one or more targets. The beads carrying active compounds can be identified and the structures of the compounds elucidated. It is also desirable to separate the beads into arrays that are geometrically compatible with robotic screening systems, for example 8.times.12 arrays or other formats such as 384 or 896-well configurations.
Current methods of bead arraying include manual picking and hydrodynamic sorting in which beads are allowed to flow though an aperture and once detected are deposited into assay wells. Manual picking is slow and tedious. Hydrodynamic methods heretofore in use have been slow and the equipment is prone to clogging. Buoyancy variations within the bead library are also known to cause problems in hydrodynamic sorting. A problem common to the prior methods is that, because the beads are extremely small, typically 300 m (0.3 mm) or smaller, there is a tendency for two or more beads, carrying different compounds, to be deposited occasionally at a single location in the array. Still another problem encountered in bead arraying is that the beads tend to be fragile, and can be broken up into fragments especially when mechanically agitated.
There is a need for a simple, rapid and reliable method and apparatus for bead arraying which reliably delivers a single bead to each point in the array. The principal object of this invention, therefore, is to provide an improved apparatus and method for selecting individual compound-bearing beads from a combinatorial library and reliably depositing individual beads into an array. It is also an object of the invention to provide an improved apparatus for bead arraying which is inexpensive, easy to use and independent of the nature of the compounds on the beads. Still another object of the invention is to avoid, or at least reduce instances in which the beads are broken up into fragments.